JP2016538057A - Drug delivery device having a needle shield with a needle cap remover - Google Patents

Abstract

The present invention is a drug delivery device (1) comprising: a housing (2) housing and holding a container (6) to which a needle (5) can be attached at its distal end, and a needle shield (4) Between the advanced position (PI) where the needle (5) is covered and the retracted position (PII) where the needle (5) extends through the distal opening (4.2) of the needle shield (4) A needle shield adapted to be movable relative to the housing (2) and a protective needle cap (7) releasably attached to cover the needle (5) prior to injection, wherein The needle shield (4) is a drug applied to move in a double motion sequence (M1, M2) between the forward position (PI) and the backward position (PII) in order to sequentially perform different operations. It relates to a delivery device.

Description

  The present invention relates to drug delivery devices.

  Many prior art drug delivery devices such as self-injectors, syringes, etc. have been developed for self-administration of drugs.

  In order to protect the needle of the drug delivery device from damage before use of the device or to protect people from needle stings, the needle of the drug delivery device is protected by a protective needle cap or a so-called rigid needle shield (abbreviated RNS). Covered.

  To prepare a drug delivery device to deliver a dose, the protective needle cap must be removed from the needle. This can be done by grasping the protective needle cap and pulling it out of the needle. Usually, this results in exposure of the needle, which is undesirable from a needle safety standpoint. To solve that problem, the needle of the drug delivery device can be covered by a needle shield or shroud so as to conceal the needle when the protective needle cap is removed.

  It is an object of the present invention to provide a drug delivery device that is easy to use, manufacture, and assemble, particularly reducing the risk of needle puncture and needle damage prior to use of the device.

  This object is achieved by a drug delivery device according to claim 1.

  Preferred embodiments of the invention are given in the dependent claims.

  In accordance with the present invention, a drug delivery device includes a housing that houses and holds a container to which a needle can be attached at a distal end thereof, a needle shield that is in an advanced position where the needle is covered, and the needle is a needle shield. A needle shield adapted to be movable relative to the housing between a retracted position extending through the distal opening and a protective needle cap releasably attached to cover the needle prior to injection. Including, where the needle shield is applied to move in a double movement sequence between an advanced position and a retracted position to sequentially perform different actions.

  The invention makes it possible to remove the protective needle cap without using any additional remover element, for example manually by hand. Furthermore, in the present invention, unintentional activation of the needle shield is avoided because the needle shield setup activation is required to prepare it for injection.

  In a possible embodiment of the invention, a first movement is provided by a respective first movement sequence of the needle shield. In the first operation, during the first motion sequence prior to injection, the needle shield is movable from the advanced or starting position to the retracted position and again to the advanced or intermediate position, whereby the needle shield releases the protective needle cap. To do. Particularly during the first movement sequence, the needle shield is applied to capture the protective needle cap at least in the retracted position, and when the needle shield returns to the advanced or starting position again, the protective needle cap is moved along the needle, Thus, it is moved away from the needle so that the protective needle cap can be removed manually or the protective needle cap falls. Thus, the present invention allows the protective needle cap to be removed without using any additional remover elements.

  In addition, a second action is provided by each second movement sequence of the needle shield. In the second operation, an injection is provided during the second movement sequence from the advance or intermediate position to the retracted position and again to the advance or end position, the needle is covered by a needle shield before and after injection, Extends only through the opening of the needle shield. After the second motion sequence, the needle shield is securely and permanently secured to the housing in the advanced or end position. Accordingly, the needle shield of the drug delivery device is comprised of two similar sequential push motion sequences of the needle shield, first a push motion sequence that removes the protective needle shield, and second, before and after injection. The two motions are met in sequence by a push-in motion sequence that allows injection including needle protection.

  According to another aspect of the present invention, a guiding arrangement for guiding the needle shield with respect to the housing is disposed between the housing and the needle shield, the guiding arrangement having the needle shield in a double motion sequence. Applied to guide. The guiding arrangement allows an essentially linear movement and thus a simple and safe guidance of the needle shield relative to the housing in order to carry out different operations, i.e. a removal operation and an injection operation in sequence.

  In one embodiment of the invention, the guiding arrangement has a labyrinth-shape with different strokes for different movement sequences. Preferably, one stroke represents one movement of the needle shield and thus one push motion sequence, so that different motion sequences are separated from each other.

  According to additional features of the invention, the guide arrangement includes a guide track and a guide arm, the guide track is formed in the housing, the guide arm is engaged on the needle shield, or vice versa. . Preferably, the guide arm includes an end that is flexible and forms a pin that cooperates with the guide track. Further, the guide arm is adapted to protrude inwardly from the needle shield and pivot about a vertical axis. Due to the flexible design of the guide arm, rotation during the linear movement of the needle shield relative to the housing is prevented. Therefore, comfort during injection is improved. The guide track includes a plurality of recesses that are arranged essentially parallel to each other and separated from each other by ribs to form different stroke guides for different movement sequences of the needle shield.

  According to another feature of the invention, each of at least two of these recesses has a labyrinth chamber having a closed end and an open end opposite to form a respective stroke for one of the motion sequences. chamber). Due to the closed recess on one side, each recess forms a chamber within which the guide arm engages at the closed end to stop the movement of the needle shield relative to the housing.

Specifically, one of the ends of the recess is closed and the opposite end is open, so that the end of the guide arm engages one of the closed ends of the recess in a different motion, During one of the double motion sequences, it is guided from one of the recesses through the open end into the adjacent recess. Such a designed labyrinth shape of the guiding arrangement allows a simple separation of the different movements of the needle shield and the pushing motion sequence.

  According to yet another embodiment, the recess is slightly curved in the region of the closed end to form a releasable rest position.

  According to another feature of the invention, in the region of one closed end of the recess, at least one of the respective ribs of the recess comprises a hook-shaped protrusion, in which the guide arm The end is securely and securely fixed to the housing in the advanced position. Thus, an easy and simple permanent lock of the needle shield relative to the housing after injection in the advanced position where the needle is covered is provided and further movement of the needle shield is prevented.

  According to a further feature of the present invention, at least two guide arrangements are provided, wherein the at least two guide arrangements are arranged opposite to each other and synchronized with each other to support safe guidance of the needle shield relative to the housing. Is done.

  According to a further embodiment, a snap arm is provided on the needle shield. The snap arm includes a locking hook at its free end for capturing the protective needle cap.

  Further scope of applicability of the present invention will become apparent from the detailed description provided hereinafter. However, although the detailed description and specific examples illustrate preferred embodiments of the present invention, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description, It should be understood that this is shown for illustrative purposes only.

  The present invention will be understood in more detail from the following detailed description and the accompanying drawings, which are provided for purposes of illustration only and therefore are not intended to limit the present invention. :

1 is a side view illustrating one embodiment of a drug delivery device in a delivery state. FIG. FIG. 6 is a side view of the drug delivery device after movement of the needle shield from the advanced position into the retracted position where the protective needle cap extends through the needle shield opening. FIG. 7 is a side view of a drug delivery device having a needle shield that reenters an advanced position where a protective needle cap extends further through an opening in the needle shield. FIG. 6 is a side view of a drug delivery device prior to injection with the needle shield in the advanced position and the protective needle cap removed. FIG. 6 is a side view of a drug delivery device during injection with the needle shield in a retracted position so that the needle extends through an opening in the needle shield. FIG. 6 is a schematic view of one embodiment of a guide arrangement comprising a guide track having a maze shape and different positions of guide arms within the guide track. FIG. 6 is a partial cross-sectional view of a drug delivery device in the area of a needle shield that includes two snap arms with locking hooks.

  Corresponding parts are marked with the same reference symbols in all figures.

  FIG. 1 shows a side view of a drug delivery device 1 in a delivery state.

  The drug delivery device 1 includes a housing 2 and a needle safety device 3. The drug delivery device 1 can be a self-injector with a container, an injection pen or syringe, such as a pre-filled syringe, or another drug container or any other application with equivalent functional principles.

  The housing 2 can be designed as a single member housing or as a multiple member housing. In the illustrated embodiment, the housing 2 includes a back housing part 2.1, a front housing part 2.2, and a support body 2.3.

  In the context of this specification, the term “rear” or “proximal” end of a component or device refers to the end closest to the user's hand or farthest from the delivery or injection site, The term “front” or “distal” or “upper” end refers to the end furthest from the user's hand or closest to the delivery or injection site.

  The different housing members can be formed as injection molded members and all members can be formed as a single unit or separated from each other. In particular, the rear housing member 2.1, the front housing member 2.2, and the support body 2.3 are formed as one injection molded member.

  The needle safety device 3 includes at least a needle shield 4. The needle shield 4 is movably mounted on the housing 2 of the drug delivery device 1 according to the first movement M1.1 of the first movement sequence M1. FIG. 1 shows the needle shield 4 in the advanced position PI. During the first movement M1.1, the needle shield 4 is movable from the forward position PI to the backward position PII (shown in FIG. 2). In the advanced position PI in the delivery state of the drug delivery device 1, the needle shield 4 is applied so as to cover the needle 5 before injection (shown in FIG. 1).

  Needle shield 4 includes a needle shield end 4.1 adapted to engage an injection site.

  As shown in FIG. 2, the housing 2 can accommodate a syringe as the container 6 and can fix the needle 5 to the distal end of the syringe. Alternatively, the needle 5 can be removable from the distal end for design choice.

  The needle safety device 3 further includes a protective needle cap 7.

  As can be seen, the needle shield 4 is movably mounted on the housing 2 by a non-releasable connection, for example by a snap-fit connection. A spring 8 biases the needle shield 4 at one end and biases the housing 2 at the other end. The needle shield 4 is applied so as to cover the needle 5 before and after the injection.

  The protective needle cap 7 is detachably mounted on the needle 5. The protective needle cap 7 is a so-called protective needle shield so as to cover the needle 5 prior to use in order to protect the needle 5 from damage during transport or movement and to keep the needle 5 sterile during the assembly process. Designed as a rigid needle shield (abbreviated RNS). The protective needle cap 7 is of a typical shape and includes an inner rubber needle shield (not shown) or a soft rubber or rubber-like core for easier and safe handling. The inner rubber needle shield is applied to accommodate and protect the needle 5.

  As shown in FIG. 2, in the retracted position PII, the needle 5 extends through the distal opening 4.2 of the needle shield 4 with the assembled protective needle cap 7.

  According to the present invention, the needle shield 4 performs a double motion sequence M1 (shown in the sequence of FIGS. 1 to 3) or M2 (shown in the sequence of FIGS. 1 to 3) between the forward position PI and the backward position PII in order to sequentially perform different operations. Applied in the sequence 3-5).

  The first movement sequence M1 is shown in the sequence of FIGS. 1-3 and represents the first operation of the drug delivery device 1 prior to injection, whereby the protective needle cap 7 is removed.

  In the first operation, during the first movement sequence M1 before injection, the needle shield 4 is moved from the advanced position PI (also referred to as the start position) to the retracted position PII (also referred to as the intermediate position) and again to the advanced position PI. So that the needle shield 4 releases the protective needle cap 7.

  In particular, during the first movement M1.1 of the first movement sequence M1, the needle shield 4 is fitted with a friction connection and / or a positive locking connection and / or a form-fitting connection. connection) is applied to capture the protective needle cap 7 at least in the retracted position PII.

  The needle shield 4 comprises at least one inwardly facing snap arm 4.4 arranged at the needle shield end 4.1, whereby the snap arm 4.4 is preferably during the first movement M1.1. Clips on the rear end of the protective needle cap 7 after the first movement M1.1 is completed. Preferably, the needle shield 4 includes a pair of snap arms 4.4 or a plurality of arms.

  Due to the snap-fit connection of the snap arm 4.4 at the rear end of the protective needle cap 7, when the needle shield 4 returns to the advanced position PI during the second movement M1.2 of the first movement sequence M1, the protective needle The cap 7 is moved along the needle 5 and thus away from the needle 5.

  As shown in FIG. 3, depending on the length of the needle shield 4 and the length of the protective needle cap 7 and the length of the second movement M1.2, the protective needle cap 7 follows the arrow R to the drug delivery device. 1 can be removed manually by hand. Alternatively, the protective needle cap 7 falls. Thus, the present invention allows the protective needle cap 7 to be removed without using any additional remover elements.

  The sequence of FIG. 4 and FIG. 5 shows the 2nd operation | movement by each 2nd movement sequence M2 of the needle shield 4. FIG. In the second operation, after removing the protective needle cap 7 during the second movement sequence M2, the needle shield 4 moves from the start or advance position PI to the retract position PII (the second movement sequence shown in FIGS. 4 and 5). M2 representing the first motion M2.1 of M2) and again to the forward position PI (representing the second motion M2.2 of the second motion sequence M2 partially shown in FIG. 6).

  During the first movement M2.1 of the second movement sequence M2, the drug delivery device 1 is placed over the injection site, whereby the needle shield 4 is moved from the advanced position PI to the retracted position PII, as a result. The needle 5 extends through the distal opening 4.2 of the needle shield 4. During the first movement M2.1, the spring 8 is tensioned by moving the needle shield 4 into the retracted position PII.

  After the injection, the drug delivery device 1 is removed. Thus, the needle shield 4 is pushed back to the advanced position PI by releasing the spring 8 during the second movement M2.2. After the second movement M2.2 and thus after the end of the second movement M2.2, the needle shield 4 is securely and permanently fixed in the advanced position PI so as to cover the needle 5 permanently.

  FIG. 6 shows a possible embodiment of a guide arrangement 9 for controlling the double movement sequence M1, M2 of the needle shield 4.

  The guide arrangement 9 is arranged between the housing 2 and the needle shield 4. The guide arrangement 9 has a labyrinth-shaped guide track 9.1 which has different strokes 9.2 to 9.3 for different movements M1.1 to M2.2 of the movement sequence M1, M2. Have. Preferably, one stroke 9.2 or 9.3 represents one movement and thus one push-in movement of the needle shield 4, and the first stroke 9.2 and the first of each of the first sequences M1 The pushing movement M1.1 represents a releasing action to release the protective needle cap 7, and the first pushing movement M2.1 of the second stroke 9.3 and the second sequence M2, respectively, enables injection. Represents a ready-for-injection operation.

  The guide arrangement 9 further includes a guide arm 9.4.

  As best seen in FIG. 2 or FIG. 5, the drug delivery device 1 includes two guiding arrangements 9 arranged opposite to each other with respect to the needle safety device 3. The guide track 9.1 is formed in the support body 2.3 of the housing 2, and the guide arm 9.4 is attached on the needle shield 4 and faces inwardly into the needle shield 4.

  The guide arm 9.4 is flexible and includes an end forming a pin 9.4.1 that cooperates with the guide track 9.1. Guide arm 9.4 is applied to pivot about a vertical axis.

  The guide track 9.1 includes a plurality of recesses 9.5 to 9.7, the plurality of recesses 9.5 to 9.7 being arranged essentially parallel to one another, by ribs 9.8 to 9.9. Separated from one another, different stroke guides for different movements M1.1 to M2.2 of the needle shield 4 are formed.

  Two of the recesses 9.6 and 9.7 are designed as labyrinth chambers having a closed end 10 and an opposite open end 11 so as to form respective strokes 9.2, 9.3. Due to the closed recesses 9.5 to 9.7 on one side, each recess forms a chamber in which the guide arm 9.4 stops movement of the needle shield 4 relative to the housing 2 into the advanced position PI. At the closed end 10.

  Thus, the rib 9.9 located in the guide track 9.1 and the open end 11 of the additional rib 12 are curved, so that the guide arm 9.4 engages them, so that the needle shield 4, the guide arm 9.4 is bent by the curved open end 11 or rib 12, so that the pin 9.4.1 of the guide arm 9.4 is ribbed in the region of the open end 11. .8 or 9.9 is guided from one of the recesses 9.5 or 9.6 into the adjacent recess 9.6 or 9.7.

  Specifically, in the first movement sequence M1, during the first movement M1.1, the guide arm 9.4 is guided from the advance or start position PI along the recess 9.5 to the open end 11 and the retracted position PII. Engage with the rib 12 at the retracted position PII and the snap arm 4.4 captures the protective needle cap 7. The guide arm 9.4 is then further guided around the rib 9.8 into the adjacent recess 9.6 during the second movement M1.2 and again the advance of the closed end 10 of the recess 9.6 or It is further guided to the intermediate position PI, whereby the first movement sequence M1 is ended and the protective needle cap 7 is released and dropped or removed.

  During the second movement sequence M2, the guide arm 9.4 is guided along a recess 9.6 that is slightly curved at the closed end 10 from the advanced or intermediate position PI, and the pins 9.. Create a releasable rest position for 4.1. Due to the curved closed end 10 of the recess 9.6, the guide arms 9.4 are each bent outwardly by further movement of the needle shield 4, and during the first movement M2.1, the recess 9.6 is bent. Re-engage the ribs 9.9 along (= pushing motion to prepare for injection). The rib 9.9 is slightly curved at the open end 11 of the recess 9.6, so that the guide arm 9.4 bends again, so that the guide arm 9.4 enters the adjacent recess 9.7. Guided.

  After the injection, the guide arm 9.4 is guided along the recess 9.7 during the second movement M2.2. At the closed end 10 of the recess 9.7, the guide arm 9.4 bends again into the hook-like projection 13 formed in the rib 9.9, so that the pin 9.4 of the guide arm 9.4 .1, and thus the needle shield 4 is permanently fixed in the forward or end position PI after the injection and thus after the second movement sequence M2.

  The described labyrinth shape of the guide arrangement 9 allows for a simple separation of the different movements of the needle shield 4 and the pushing movement sequences M1 and M2.

  Furthermore, the needle shield 4 of the drug delivery device 1 provides two similar successive push-motion sequences M1, M2, in particular a first push-motion sequence M1 that removes the protective needle cap 7, and protection of the needle before and after injection. The two movements are fulfilled in sequence by means of a second push-in movement sequence M2 that allows for injection including.

  FIG. 7 shows the snap arm 4.4 of the needle shield 4 in more detail.

The term “drug” or “agent” as used herein means a pharmaceutical formulation comprising at least one pharmaceutically active compound,
Here, in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da and / or a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or fragment thereof, hormone Or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compounds,
Here, in a further embodiment, the pharmaceutically active compound is diabetic or diabetes related complications such as diabetic retinopathy, thromboembolism such as deep vein thromboembolism or pulmonary thromboembolism, acute coronary syndrome (ACS), useful for the treatment and / or prevention of angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis,
Here, in a further embodiment, the pharmaceutically active compound comprises at least one peptide for the treatment and / or prevention of diabetes-related complications such as diabetes or diabetic retinopathy,
Here, in a further embodiment, the pharmaceutically active compound is at least one human insulin or human insulin analogue or derivative, glucagon-like peptide (GLP-1) or analogue or derivative thereof, or exendin-3 or exendin -4 or exendin-3 or analogs or derivatives of exendin-4.

  Insulin analogues include, for example, Gly (A21), Arg (B31), Arg (B32) human insulin; Lys (B3), Glu (B29) human insulin; Lys (B28), Pro (B29) human insulin; Asp ( B28) human insulin; proline at position B28 is replaced with Asp, Lys, Leu, Val, or Ala, and at position B29, human insulin where Lys may be replaced with Pro; Ala (B26) human insulin; Des (B28-B30) human insulin; Des (B27) human insulin, and Des (B30) human insulin.

  Insulin derivatives include, for example, B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28- N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N- (N-palmitoyl) -Des (B30) human insulin; B29-N- (N-ritocryl-γ-glutamyl) -des (B30) human insulin; B29-N- (ω- Carboxymethyl hepta decanoyl) -des (B30) human insulin, and B29-N- (ω- carboxyheptadecanoyl) human insulin.

  Exendin-4 is, for example, H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu Exendin-4 (1-39, which is a peptide of the sequence -Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 ).

Exendin-4 derivatives are, for example, compounds of the following list:
H- (Lys) 4-desPro36, desPro37 exendin-4 (1-39) -NH2,
H- (Lys) 5-desPro36, desPro37 exendin-4 (1-39) -NH2,
desPro36 exendin-4 (1-39),
desPro36 [Asp28] exendin-4 (1-39),
desPro36 [IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, IsoAsp28] Exendin- (1-39),
desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14Trp (O2) 25, IsoAsp28] Exendin-4 (1-39); or desPro36 [Asp28] Exendin-4 (1-39),
desPro36 [IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, IsoAsp28] Exendin- (1-39),
desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O 2) 25, IsoAsp 28] Exendin-4 (1-39),
(Wherein the group -Lys6-NH2 may be attached to the C-terminus of the exendin-4 derivative);

Or an exendin-4 derivative of the following sequence:
desPro36 exendin-4 (1-39) -Lys6-NH2 (AVE0010),
H- (Lys) 6-desPro36 [Asp28] Exendin-4 (1-39) -Lys6-NH2,
desAsp28Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39) -Lys6-NH2,
H-desAsp28Pro36, Pro37, Pro38 [Trp (O2) 25] exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Met (O) 14, Asp28] exendin-4 (1-39) -Lys6-NH2,
desMet (O) 14, Asp28Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2;
desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Lys6-desPro36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -Lys6-NH2,
H-desAsp28, Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25] exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (S1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2;
Or a pharmaceutically acceptable salt or solvate of any one of the aforementioned exendin-4 derivatives.

  The hormones include, for example, gonadotropin (folytropin, lutropin, corion gonadotropin, menotropin), somatropin (somatropin), desmopressin, telluripressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin, etc., Rote Liste, 2008 Pituitary hormones or hypothalamic hormones or regulatory active peptides and antagonists thereof.

  Polysaccharides include, for example, glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin, or ultra low molecular weight heparin, or derivatives thereof, or sulfated forms of the above-described polysaccharides, such as polysulfated forms, and Or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is sodium enoxaparin.

  Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins that share a basic structure. These are glycoproteins because they have sugar chains attached to amino acid residues. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (including only one Ig unit), and the secretory antibody is also a dimer having two Ig units such as IgA, teleost It can also be a tetramer with 4 Ig units, such as IgM, or a pentamer with 5 Ig units, like mammalian IgM.

  An Ig monomer is a “Y” -shaped molecule composed of four polypeptide chains, two identical heavy chains and two identical light chains joined by a disulfide bond between cysteine residues. It is. Each heavy chain is about 440 amino acids long and each light chain is about 220 amino acids long. Each heavy and light chain contains intrachain disulfide bonds that stabilize these folded structures. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (eg, variable or V, and constant or C) based on their size and function. They have a characteristic immunoglobulin fold that creates a “sandwich” shape in which two β-sheets are held together by the interaction between conserved cysteines and other charged amino acids.

  There are five types of mammalian Ig heavy chains represented by α, δ, ε, γ and μ. The type of heavy chain present defines the isotype of the antibody, and these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Different heavy chains differ in size and composition, α and γ contain about 450 amino acids, δ contain about 500 amino acids, and μ and ε have about 550 amino acids. Each heavy chain has two regions: a constant region (C _H ) and a variable region (V _H ). In one species, the constant region is essentially the same for all antibodies of the same isotype, but different for antibodies of different isotypes. Heavy chains γ, α, and δ have a constant region composed of three tandem Ig domains and a hinge region to add flexibility, and heavy chains μ and ε are four immunoglobulins -It has a constant region composed of domains. The variable region of the heavy chain is different for antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

  In mammals, there are two types of immunoglobulin light chains, denoted λ and κ. The light chain has two consecutive domains, one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211-217 amino acids. Each antibody has two light chains that are always identical, and there is only one type of light chain κ or λ for each mammalian antibody.

  Although the general structure of all antibodies is very similar, the unique properties of a given antibody are determined by the variable (V) region, as detailed above. More specifically, three variable loops for each light chain (VL) and three variable loops in the heavy chain (HV) are involved in antigen binding, ie its antigen specificity. These loops are called complementarity determining regions (CDRs). Since CDRs from both the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that determines the final antigen specificity, not either alone.

  “Antibody fragments” comprise at least one antigen-binding fragment as defined above and exhibit essentially the same function and specificity as the complete antibody from which the fragment is derived. Limited protein digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one complete light chain and about half the heavy chain, are antigen-binding fragments (Fabs). A third fragment that is equivalent in size but contains a carboxyl terminus at half the positions of both heavy chains with interchain disulfide bonds is a crystallizable fragment (Fc). Fc includes a carbohydrate, a complementary binding site, and an FcR binding site. Limited pepsin digestion yields a single F (ab ') 2 fragment containing both the Fab piece and the hinge region containing the H-H interchain disulfide bond. F (ab ') 2 is divalent for antigen binding. The disulfide bond of F (ab ') 2 can be cleaved to obtain Fab'. In addition, the variable regions of the heavy and light chains can be condensed to form a single chain variable fragment (scFv).

  Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Examples of acid addition salts include HCl or HBr salts. The basic salt is, for example, a cation selected from alkali or alkaline earth such as Na +, or K +, or Ca2 +, or ammonium ions N + (R1) (R2) (R3) (R4) (wherein R1 ~ R4 are independently of each other: hydrogen, optionally substituted C1-C6 alkyl group, optionally substituted C2-C6 alkenyl group, optionally substituted C6-C10 aryl group, or optionally substituted C6- Meaning a C10 heteroaryl group). Additional examples of pharmaceutically acceptable salts can be found in “Remington's Pharmaceutical Sciences” 17th edition, Alfonso R. et al. Gennaro (eds.), Mark Publishing Company, Easton, Pa. U. S. A. 1985, and Encyclopedia of Pharmaceutical Technology.

  A pharmaceutically acceptable solvate is, for example, a hydrate.

  Modifications (additions and / or deletions) of various components of the apparatus, methods, and / or embodiments and embodiments described herein may be made without departing from the full scope and spirit of the invention. Those skilled in the art will appreciate that the invention includes such modifications and any equivalents thereof.

DESCRIPTION OF SYMBOLS 1 Drug delivery device 2 Housing 2.1 Rear housing member 2.2 Front housing member 2.3 Support body 3 Needle safety device 4 Needle shield 4.1 Needle shield end 4.2 Distal opening 4.4 Snap arm 5 Needle 6 Container 7 Protective needle cap 8 Spring 9 Guide arrangement 9.1 Guide track 9.2, 9.3 Stroke 9.4 Guide arm 9.4.1 Pin 9.5-9.7 Recess 9.8, 9. 9 Rib 10 Closed end of recess 11 Open end of rib 12 Additional rib 13 Hook-like protrusion M1 First motion sequence M1.1 First motion of first motion sequence M1.2 First motion sequence 2 movements M2 2nd movement sequence M2.1 1st movement of 2nd movement sequence M2.2 2nd movement of 2nd movement sequence PI Advance position PII reverse position R arrow

Claims (13)

A drug delivery device (1) comprising:
A housing (2) containing and holding a container (6) to which a needle (5) can be attached at its distal end;
The housing (between the advanced position (PI) where the needle (5) is covered and the retracted position (PII) where the needle (5) extends through the distal opening (4.2) of the needle shield (4). A needle shield (4) adapted to be movable relative to 2);
And a protective needle cap (7) releasably attached to cover the needle (5) prior to injection, wherein the needle shield (4) is in an advanced position (PI) to perform different operations in sequence. ) And a retracted position (PII) applied to move in a double motion sequence (M1, M2),
In the first action, during the first double motion sequence (M1) before injection from the forward position (PI) to the backward position (PII) and again to the forward position (PI), the needle shield (4) Is applied to release the protective needle cap (7) and between the housing (2) and the needle shield (4) guide arrangement (9) for guiding the needle shield (4) relative to the housing (2) The drug delivery device is adapted to guide the needle shield (4) in a double motion sequence (M1, M2). In the second action, after the second movement sequence (M2) from the forward position (PI) to the backward position (PII) and again to the forward position (PI), the needle shield (4) is moved to the forward position (PI). Securely and securely fixed to the housing (2) with
The drug delivery device (1) according to claim 1. The guiding arrangement (9) has a maze shape with different strokes (9.2, 9.3) for different movements,
Drug delivery device (1) according to claim 1 or 2. The guide arrangement (9) includes a guide track (9.1) and a guide arm (9.4), the guide track (9.1) being formed in the housing (2), the guide arm (9.4) Is attached on the needle shield (4),
The drug delivery device (1) according to any one of claims 1 to 3. The guide arm (9.4) is flexible and includes an end forming a pin (9.4.1) cooperating with the guide track (9.1),
The drug delivery device (1) according to any one of claims 1 to 4. The guide track (9.1) comprises a plurality of recesses (9.5-9.7), which are arranged essentially parallel to one another and are provided by ribs (9.8, 9.9). Separated from each other,
A drug delivery device (1) according to any one of the preceding claims. Each of at least two of the recesses (9.6, 9.7) has a closed end (10) and an opposite open end (11) so as to form a respective stroke (9.2, 9.3). Designed as a maze chamber,
The drug delivery device (1) according to claim 6. One end (10) of the recess (9.5-9.7) is closed and the opposite end (11) is open, so that the end of the guide arm (9.4) is , Engages one of the closed ends (10) of the recesses (9.5 to 9.7) in different motions and during one of the double motion sequences (M1, M2), the recesses (9.5 to 9. 6) guided from one side through the open end (11) into the adjacent recess (9.6-9.7),
A drug delivery device (1) according to claim 6 or 7. The recess (9.5-9.7) is slightly curved in the region of the closed end (10),
A drug delivery device (1) according to any one of claims 6-8. Within the region of one closed end (10) of the recess (9.7), at least one of the respective ribs (9.9) of the recess (9.7) has a hook-shaped projection (13). including,
A drug delivery device (1) according to claim 9. The guide arm (9.4) projects inward from the needle shield (4) and is adapted to pivot about a vertical axis.
The drug delivery device (1) according to any one of claims 4 to 10. A snap arm (4.4) is provided that includes a locking hook at its free end,
A drug delivery device (1) according to any one of the preceding claims. At least two guide arrangements (9) arranged opposite each other are provided;
A drug delivery device (1) according to any one of the preceding claims.

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